Occluded Hemisphere Research Articles

Asymmetry of Lacunae between Brain Hemispheres Is Associated with Atherosclerotic Occlusions of Middle Cerebral Artery.

Patients with uni-MCAO were retrospectively observed. Imaging characteristics, including lacunae, white matter hyperintensities (WMH), enlarged perivascular spaces (EPVS), and cerebral microbleeds (CMBs), were compared between the hemisphere ipsilateral to the MCAO and the contralateral hemisphere. A total of 219 patients (median age 57 years; 156 males) were enrolled. Compared with the contralateral side, increased quality of lacunae (median, IQR, 0, 2 vs. 0, 1; p < 0.001) and elevated CSVD score (median, IQR, 0, 1 vs. 0, 1; p = 0.004) were found in the occluded hemisphere. No significant differences were shown for WMH, EPVS, and CMBs. Uni-MCAO has a higher prevalence of lacunae in the ipsilateral hemisphere. However, no interhemispheric differences in WMH, EPVS, or CMBs were found.

Validity of venous phase delay assessment in balloon occlusion test of internal carotid artery.

The aim of the present study was to investigate the utility of venous phase delay assessment to evaluate the balloon occlusion test (BOT) of the internal carotid artery (ICA). A total of 38 patients who received BOT of the ICA were included in this retrospective study. Clinical examination and venous phase assessment were performed in all patients to evaluate their suitability for the evaluation of the BOT of the ICA. The venous phase delay assessment compared the venous phase of supratentorial and infratentorial structures between hemispheres. Venous phase delay was defined as the time lag for opacification of the first cortical vein between the occluded hemisphere and the hemisphere examined. The results of the clinical examination and the venous phase delay assessment were compared. In most patients negative on clinical examination, the venous phase delay was no more than 2 sec, while for most patients positive on clinical examination, the delay was >2 sec. All patients with a venous phase delay of >4 sec had a positive clinical result. The present results indicated that venous phase delay assessment is a reliable method for evaluating BOT of the ICA, and in those with a delay of <2 sec, parent vessel occlusion of the ICA, which may be used as a pre-operative procedure prior to tumor resection for patients suffering from neck or skull-base tumors, was considered safe.

Abstract 204: Regional Hypoperfusion is Associated with Cortical Thinning in Asymptomatic Carotid Artery Disease

Objective: Cortical thinning has been reported in patients with cerebrovascular disease and degenerative dementia, but the direct impact of regional hypoperfusion on cortical pathology has been difficult to establish. We examined the association between regional cerebral blood flow (rCBF) and regional cortical thickness (rCT) in a cohort of patients with unilateral high-grade internal carotid artery (ICA) disease without history of stroke. Methods: Twenty-seven patients age 73±10yrs, 11F with unilateral ICA stenosis ≥80% or occlusion but no stroke underwent MRI, including high resolution T1 (MPRAGE) and tissue specific pseudocontinuous arterial spin labeling (ts-pCASL) to assess cortical thickness and gray matter resting CBF. Cortical thickness was measured in each hemisphere in the primary motor cortex (M1--Brodmann Area 4) by a blinded investigator using Freesurfer software ( http://surfer.nmr.mgh.harvard.edu/ ), and in visual cortex (V1, Brodmann area 17) as a control for nonspecific effects in the posterior circulation. Paired t-tests were used to assess hemispheral asymmetry for rCBF and for rCT in M1 on the occluded vs unoccluded side. Linear regression was used to predict the effect of rCBF on rCT in M1 on the occluded side. Results: Cortex was 0.08mm thinner on the side of ICA occlusion in M1 (95%CI=0.04-0.11, p=0.0003). There was no rCT asymmetry in V1 (p=.276). rCBF was 9.3 ml/100gm*min -1 lower in M1 of the occluded hemisphere (95%CI=5.1-13.5, p&lt;.0001). Cortical blood flow in M1 was a significant predictor of cortical thickness in M1 on the side of the occluded ICA (adj R 2 =.128, p=.038). Conclusion: Cortical thinning occurred in M1 on the side of carotid occlusion in the absence of stroke, and correlated with lower rCBF. Brodmann area 4 was chosen to represent the distal field of the carotid artery. Our finding demonstrates an important effect of chronically reduced blood flow on brain pathology, and suggests that a broader definition of “symptomatic” carotid artery disease may be needed.

Measurement of cortical thickness asymmetry in carotid occlusive disease.

Despite being considered an important anatomical parameter directly related to neuronal density, cortical thickness is not routinely assessed in studies of the human brain in vivo. This paucity has been largely due to the size and convoluted shape of the human cortex, which has made it difficult to develop automated algorithms that can measure cortical thickness efficiently and reliably. Since the development of such an algorithm by Fischl and Dale in 2000, the number of studies investigating the relationship between cortical thickness and other physiological parameters in the brain has been on the rise. There have been no studies however that have validated cortical asymmetry against known vascular anatomy. To this aim, using high-resolution MRI, we measured cortical thickness and volume in the primary motor (M1) and primary visual (V1) cortex in patients with unilateral, high-grade carotid occlusive disease (n = 29, age = 74 ± 10 years). These regions were selected based on the hypothesis that there will be thinning of the cortical thickness of M1 in the territory supplied by the occluded carotid artery, whereas V1 will show no asymmetry since its blood supply is provided by unaffected posterior arteries. To test for an effect of handedness, cortical thickness and volume were also measured in healthy volunteers (n = 8, age = 37 ± 13 years). In patients, we found thinner cortex in M1 on the occluded side (mean = 2.07 ± 0.19 mm vs 2.15 ± 0.20 mm, p = 0.0008) but no hemispheric difference in V1 (1.80 ± 0.17 mm in occluded vs 1.78 ± 0.16 mm in unoccluded, p = 0.31). Although the mean cortical volume of M1 in the occluded hemisphere was also lower, the difference did not reach statistical significance (p = 0.09). Similarly, in healthy controls, the results showed no hemispheric asymmetry in either cortical thickness or volume in either region (p > 0.1). To test for an orientation bias in the method, the analysis was repeated with images flipped from neurological to radiological orientation. While the algorithm did not yield identical results for the two orientations, the effect did not alter the findings of the study. These results provide a method for within-subject validation of a pathophysiological effect of carotid occlusive disease on the human cortex and warrant further investigation for underlying mechanisms.

Abstract W P170: Hemodynamic Effects in Carotid Occlusion Using Arterial Spin Labeling and Transcranial Doppler

Background: High grade carotid stenosis produces hemodynamic effects on the brain, but the relationship between cerebral autoregulation, absolute CBF and neurovascular coupling has not been well-delineated. Methods: Twelve subjects (age 74±9, 3F) with unilateral ICA stenosis (80-100% occluded) but no infarct (asymptomatic or TIA only) underwent dynamic cerebral autoregulation (DCA) testing with transcranial Doppler by comparing phase shift (PS) of spontaneous oscillations in blood pressure (measured with finger photoplethysmography (Finapres)) versus MCA flow velocities at frequencies .06-.12 Hz using transfer function analysis, lower degree of PS indicating worse autoregulation.Neurovascular coupling was assessed by amplitude of absolute increase in CBF in bilateral Brodman area (BA) 4 during a bilateral repetitive hand closure task using continuous arterial spin labeling (CASL) MRI. Four activation (ON) periods were averaged and subtracted from 4 rest (OFF) periods. Resting CBF for each hemisphere’s motor cortex was determined by averaging the OFF periods. Results: All subjects showed: 1) hemispheric asymmetry in baseline CBF with the occluded side being on average 25mL/100g*min (+/- 14 mL/100g*min) lower than the unoccluded hemisphere. 2) hemispheric asymmetry in motor activation: unoccluded hemisphere average activation (mean_CBF_ON - mean_CBF_OFF) in BA4 was 23.7mL/100g*min, representing a 21% increase in local CBF due to activation; occluded hemisphere mean activation was 14 mL/100g*min, representing 18% percent increase in local CBF. 3) Hemispheric asymmetry in DCA, PS=33.1 deg ± 31 on the occluded side vs. 43.5 deg±23 on the non-occluded side. Both the hemispheral difference in baseline CBF (impaired flow) and the difference in DCA measurement (impaired autoregulation) were good predictors of the lower activation (neurovascular coupling) on the occluded hemisphere: R 2 = 0.85 and 0.80, respectively. Conclusion: Both impaired resting CBF and impaired cerebral autoregulation appear to contribute to decreased neurovascular coupling in carotid artery occlusive disease, representing a potential mechanism for occult neuronal dysfunction such as mild cognitive impairment in this patient population.

Balloon occlusion test of the internal carotid artery: correlation with stump pressure and 99mTc-HMPAO SPECT

To evaluate the correlation of stump pressure during balloon occlusion test and relative cerebral blood flow (relative CBF) as measured by 99mTc-hexamethylpropyleneamine oxime (99mTc-HMPAO) single-photon emission computed tomography (SPECT) after test occlusion. Balloon occlusion test of the internal carotid artery (ICA) was performed in 25 patients. The count ratio of occluded hemisphere to non-occluded hemisphere was calculated on 99mTc-HMPAO SPECT. The ratio of mean stump pressure to mean arterial pressure during carotid occlusion during the balloon occlusion test was compared with the count ratio of 99mTc-HMPAO SPECT. Two patients failed to tolerate even brief carotid occlusion. The other 23 patients showed no ischemic deficit during occlusion of the ICA. In 13 of these 23 patients, the ratios of mean stump pressure to mean arterial pressure were more than 50%, and the count ratios on SPECT were more than 85%. In 10 of 23 patients, the ratios of mean stump pressure to mean arterial pressure were less than 50%, and the count ratios on SPECT were variable. Maintenance of a mean stump pressure of 50% or more of the mean systemic pressure during test occlusion indicates adequate cerebral blood flow during carotid occlusion.

ADAMTS-1 and -4 are up-regulated following transient middle cerebral artery occlusion in the rat and their expression is modulated by TNF in cultured astrocytes

ADAMTS ( a disintegrin and metalloproteinase with thrombo spondin motifs) enzymes are a recently described group of metalloproteinases. The substrates degraded by ADAMTS-1, -4 and -5 suggest that they play a role in turnover of extracellular matrix in the central nervous system (CNS). ADAMTS-1 is also known to exhibit anti-angiogenic activity. Their main endogenous inhibitor is tissue inhibitor of metalloproteinases (TIMP)-3. The present study was designed to investigate ADAMTS-1, -4 and -5 and TIMP-3 expression after experimental cerebral ischaemia and to examine whether cytokines known to be up-regulated in stroke could alter their expression by astrocytes in vitro. Focal cerebral ischaemia was induced by transient middle cerebral artery occlusion in the rat using the filament method. Our results demonstrate a significant increase in expression of ADAMTS-1 and -4 in the occluded hemisphere but no significant change in TIMP-3. This was accompanied by an increase in mRNA levels for interleukin (IL)-1β, IL-1 receptor antagonist (IL-1ra) and tumour necrosis factor (TNF). ADAMTS-4 mRNA and protein were up-regulated by TNF in primary human astrocyte cultures. The increased ADAMTS-1 and -4 in experimental stroke, together with no change in TIMP-3, may promote ECM breakdown after stroke, enabling infiltration of inflammatory cells and contributing to brain injury. In vitro studies suggest that the in vivo modulation of ADAMTS-1 and -4 may be controlled in part by TNF.

Balloon Test Occlusion with Perfusion CT Imaging Utilizing Intraarterial Contrast Injection

Balloon Test Occlusion (BTO) is performed to evaluate the collateral flow when a permanent therapeutic occlusion of unilateral carotid artery is planned. BTO with neurological evaluation alone, however, has a rather high false negative rate. In order to improve the sensitivity, several adjunctive procedures such as induced hypotension or cerebral blood flow (CBF) measurement with various modalities have been combined. Perfusion CT (PCT) is another imaging modality that is mainly used for the diagnosis of acute stroke. In this study, we evaluate the efficacy and the safety of BTO combined with PCT in the same procedure utilizing intraarterial contrast injection from the catheter. Seven patients underwent BTO with PCT in our institution. All the procedures were performed in the angio/CT combination suite. BTO was performed in the usual fashion and when the patient passed the 30 minutes' BTO clinically, PCT was performed subsequently. Contrast material was injected from a Pig Tail catheter placed in the ascending aorta. The obtained data were transferred to a workstation and perfusion maps of CBF, cerebral blood volume (CBV), and time to peak (TTP) were generated using software. In three patients, single photon emission CT (SPECT) was also obtained with administering 99 mTc-ethyl cysteinate dimer (99 mTc-ECD) intravenously during BTO. Although all the patients had passed the BTO clinically, the CBF maps of three patients revealed significant decrease in the occluded hemisphere. There was no procedure-related morbidity. PCT using intraarterial contrast injection during BTO was performed successfully and safely. Intraarterial injection allowed us to obtain excellent time-attenuation curves by utilizing less contrast material and less radiation doze.

Probability of metabolic tissue recovery after thrombolytic treatment of experimental stroke: a magnetic resonance spectroscopic imaging study in rat brain.

The effect of thrombolytic therapy on metabolic changes was studied in rats submitted to thromboembolic stroke. Reperfusion was initiated at three different time points, 1.5, 3, and 4.5 hours after embolism (n = 3 each), by injection of recombinant tissue-type plasminogen activator (rt-PA). Recovery was observed during 5 hours of reperfusion using perfusion-weighted images and a two-dimensional 1H magnetic resonance spectroscopic imaging (MRSI) technique. Temporal evolution of the cerebral metabolites lactate and N-acetyl-aspartate (NAA) was determined. To analyze the chances of metabolic tissue recovery, the outcome of treatment, defined by a reversal of lactate concentration, was compared with the lactate intensity before treatment. In untreated animals (n = 4), clot embolism resulted in a drop of perfusion signal intensity in the occluded hemisphere followed by an increase of lactate concentration and a decrease of NAA that persisted throughout the observation period. Thrombolysis partially restored blood flow, but the mean lactate concentration decreased only slightly after successful lysis in animals treated 1.5 hours after embolism. If treatment was initiated later, no decline of lactate level was observed. Five hours after initiation of thrombolysis, the average tissue lactate amounted to 95 +/- 6, 111 +/- 17, and 139 +/- 60% of the early ischemic value (40 minutes after embolization) if treatment began 1.5, 3, and 4.5 hours after embolism, respectively. The NAA level declined slightly but never showed a recovery after rt-PA treatment. In individual pixels, the probability of metabolic tissue recovery clearly declined with increasing lactate concentration before thrombolysis. Interestingly, this probability was independent of treatment delay, but the number of pixels with low lactate declined with increasing ischemia time. Potential clinical applications of MRSI include monitoring of therapeutic intervention as well as support for prognosis of outcome after rt-PA treatment.

Preliminary evaluation of [1-11C]octanoate as a PET tracer for studying cerebral ischemia: a PET study in rat and canine models of focal cerebral ischemia.

Octanoate is taken up into the brain and is converted in astrocytes to glutamine through the TCA cycle after beta-oxidation. We speculate that [1-11C]octanoate may be used as a tracer for astroglial functions and/or fatty acid metabolism in the brain and may be useful for studying cerebral ischemia. In the present study we investigated brain distribution of [1-11C]octanoate and compared it with cerebral blood flow (CBF) by using rat and canine models of middle cerebral artery (MCA) occlusion and a high resolution PET. In rats brain distribution of [15O]H2O measured 1-2 h and 5-6 h after insult was compared with that of [1-11C]octanoate measured 3-4 h after insult. Radioactivity ratios of lesioned to normal hemispheres determined with [15O]H2O were lower than those determined with [1-11C]octanoate. These results were confirmed by a study on a canine model of MCA-occlusion. Twenty-four hours after insult, CBF decreased in the MCA-territory of the occluded hemisphere, whereas normal or higher accumulation of [1-11C]octanoate was observed in the ischemic regions. The uptake of [1-11C]octanoate-derived radioactivity therefore increased relative to CBF in the ischemic regions, indicating that [1-11C]octanoate provides functional information different from CBF. In conclusion, we found that [1-11C]octanoate is a potential radiopharmaceutical for studying the pathophysiology of cerebral ischemia.

Focal cerebral ischemia-induced escape deficit in rats is ameliorated by a reversible inhibitor of monoamine oxidase-a: implications for a novel animal model of post-stroke depression.

The present investigation was conducted to examine whether a reversible inhibitor of monoamine oxidase (MAO)-A, T-794, affects the shuttle-box escape deficit induced by transient middle cerebral artery (MCA) occlusion (MCAO). MCA-occluded and sham-operated rats (surgery on day 0) were subjected to daily shuttle-box session from day 7 to 9 (training series) and from day 13 to 15 (test series) and received twice daily administration of T-794 (10 mg/kg p.o., b.i.d.) or vehicle from the evening of day 9. In the final shuttle-box session of test series (day 15), while MCA-occluded-vehicle-treated rats showed significantly more escape failures than sham-operated-vehicle-treated rats, the failures made by MCA-occluded rats were significantly decreased by T-794 to the level of the sham-operated group. Additionally, biochemical examination was conducted after behavioral evaluation to examine possible involvement of the brain monoamine system in the observed behavioral syndrome. In occluded hemisphere of MCA-occluded rats, catecholamine levels were decreased and ratios of deaminated metabolite to corresponding monoamine were increased compared with the respective values of the sham-operated group, and these changes were reversed by T-794. Results are discussed in terms of possible relevance of the MCAO-induced escape deficit to post-stroke depression.

Effect of nicardipine on cerebral blood flow in hypertensive patients with internal carotid artery occlusion: A PET study

The objective of this study was to elucidate the effect of intravenous administration of nicardipine on the cerebral blood flow of hypertensive patients with internal carotid artery occlusion (ICAO). Six patients with ICAO and 10 normal individuals were examined by positron emission tomography. The cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral metabolic rate of oxygen, oxygen extraction fraction (OEF) and CBF/CBV ratio were evaluated for each vascular territory and each hemisphere, and the interhemispheric asymmetry index of each parameter was also calculated. Nicardipine was administered intravenously to each patient, and the changes in CBF (DeltaCBF%) and in blood pressure (DeltaBP) were examined. After the administration of nicardipine, the CBF was significantly increased in the patient hemisphere and was unchanged in the occluded hemisphere. Stepwise regression analysis disclosed that the DeltaBP and asymmetry index of OEF were significantly correlated with the DeltaCBF% in the occluded hemisphere. These results suggest that CBF is unchanged or increased in ICAO patients after nicardipine administration, but that excessive reduction of blood pressure may lead to CBF decrease in the patients with marked hemodynamic imbalance between the occluded and patent hemispheres. These results suggest that it is advisable not to reduce blood pressure excessively in these patients in the treatment of perioperative or acute hypertension with calcium antagonist.

Balloon Test Occlusion with Perfusion CT Imaging Utilizing Intraarterial Contrast Injection

Balloon Test Occlusion (BTO) is performed to evaluate the collateral flow when a permanent therapeutic occlusion of unilateral carotid artery is planned. BTO with neurological evaluation alone, however, has a rather high false negative rate. In order to improve the sensitivity, several adjunctive procedures such as induced hypotension or cerebral blood flow (CBF) measurement with various modalities have been combined. Perfusion CT (PCT) is another imaging modality that is mainly used for the diagnosis of acute stroke. In this study, we evaluate the efficacy and the safety of BTO combined with PCT in the same procedure utilizing intraarterial contrast injection from the catheter. Seven patients underwent BTO with PCT in our institution. All the procedures were performed in the angio/CT combination suite. BTO was performed in the usual fashion and when the patient passed the 30 minutes' BTO clinically, PCT was performed subsequently. Contrast material was injected from a Pig Tail catheter placed in the ascending aorta. The obtained data were transferred to a workstation and perfusion maps of CBF, cerebral blood volume (CBV), and time to peak (TTP) were generated using software. In three patients, single photon emission CT (SPECT) was also obtained with administering 99mTc-ethyl cysteinate dimer (99mTc-ECD) intravenously during BTO. Although all the patients had passed the BTO clinically, the CBF maps of three patients revealed significant decrease in the occluded hemisphere. There was no procedure-related morbidity. PCT using intraarterial contrast injection during BTO was performed successfully and safely. Intraarterial injection allowed us to obtain excellent time-attenuation curves by utilizing less contrast material and less radiation doze.

Effect of superoxide dismutase on acute reperfusion injury of the rabbit brain.

To study the involvement of free oxygen radicals of the blood-brain barrier (BBB) disruption during early reperfusion, we isolated the distal internal carotid artery, and the middle and anterior cerebral arteries via the transorbital approach in anesthetized rabbits. Using radiolabeled microspheres, regional cerebral blood flow (rCBF) was measured before, during and after 1-hour unilateral occlusion of these vessels. Fifty-five minutes after ischemia, animals received intravenous saline placebo (control), superoxide dismutase (SOD) at 8 mg/kg = 30,000 U/kg, or weakened superoxide dismutase (wSOD) at 8 mg/kg = 30,000 U/kg. Integrity of the BBB was assessed by leakage of Evan's Blue-albumin dye (EB-albumin dye), which was given at 15 minutes of reperfusion and allowed to circulate for an additional hour. In the control and wSOD-treated groups, rCBF decreased (26% and 40% of control, respectively) within the blue-tinted tissue of the occluded hemisphere during ischemia; hyperemia was observed during early reperfusion. In the control and wSOD-treated groups, EB-albumin dye leakage across the BBB increased 49% within the occluded hemisphere. However, within the SOD-treated group, the BBB showed minimal dye leakage even though rCBF of the occluded hemisphere (so-called blue-tinted tissue) decreased by 38% during ischemia. We conclude that 1-hour focal cerebral ischemia and reperfusion produce a vascular endothelial injury at the BBB. Since SOD administration showed significant protection, free-oxygen-radical production during early reperfusion is associated with breakdown of the BBB to large molecules.

Hemodynamics in internal carotid artery occlusion examined by positron emission tomography.

Using positron emission tomography in nine patients with minor strokes, unilateral internal carotid artery occlusion, and good collateral circulation through the anterior portion of the circle of Willis, we analyzed regional cerebral blood flow, cerebral metabolic rate of oxygen, oxygen extraction fraction, and cerebral blood volume. These studies allowed quantification of the regional hemodynamic status, especially in relation to watershed areas. Compared with eight normal controls, the patients had significantly (p less than 0.01) decreased regional cerebral blood flow in the middle cerebral artery territory and the surrounding watershed areas of the occluded hemisphere. The oxygen extraction fraction rose with the distance from the anterior portion of the circle of Willis, attaining the highest value in the superior parietal and posterior temporo-occipital watershed area. A concomitant decrease in the cerebral blood flow/cerebral blood volume ratio suggested reduction in the mean blood flow velocity, whereby elevated blood viscosity would be more liable to reduce cerebral blood flow. These findings suggest hemodynamic vulnerability of the watershed areas after internal carotid artery occlusion in persons with good collateral circulation through the anterior portion of the circle of Willis. Our results also emphasize the importance of systemic hemodynamic factors such as blood pressure and circulating blood volume in the genesis of watershed infarction.

Omental transposition or transplantation to the brain and superficial temporal artery--middle cerebral artery anastomosis in preventing experimental cerebral ischaemia.

Transposition of lengthened omentum to the brain surface, transplantation of an omental graft, or superficial temporal artery--middle cerebral artery anastomosis were performed in dogs prior to transcranial occlusion of the ipsilateral middle cerebral artery at its origin, including the bifurcation of the internal carotid artery. Both omentum and by-pass were able to reduce the changes in cerebral blood flow, somatosensory evoked responses, cerebral water and electrolyte content, consequent to the ischaemic insult. In the experimental conditions adopted in this study, the effect of omental transposition in maintaining high levels of flow throughout the entire occluded hemisphere was more marked compared to that resulting from the other methods, while the onset of ischaemic cerebral oedema was affected approximately at the same degree by all procedures. The results point to the role of the transposed omentum in providing an effective collateral circulation to the ischaemic brain.

Effect of transient ischemia on monoamine levels in the cerebral cortex of gerbils.

Abstract— Cortical monoamine changes during ischemic episodes of varied duration and their sequence of changes following cerebral reperfusion were studied in the gerbil. Forty‐one percent of 280 animals exhibited signs of cerebral hemispheric ischemia (stroke) after unilateral common carotid artery occlusion. Norepinephrine (NE) levels decreased after 60 min in the occluded hemisphere of stroked animals but dopamine (DA) levels were unaltered. S‐Hydroxytryptamine (5‐HT) levels became bilaterally reduced in both stroked and non‐stroked animals as soon as S min after occlusion.Upon reperfusion after periods of 30 or 60 min of occlusion there was a bilateral rebound increase of cortical NE and DA levels to well above control values in stroked and non‐stroked animals. 5‐HT levels remained reduced in both groups.Results suggest disorder of monoamine metabolism in ischemic brain which persists during the early reperfusion period, perhaps contributing to deficits in neurological function.Monoamine changes in contralateral non‐ischemic hemispheres both during the occlusion and reperfusion periods are thought further evidence of diaschisis.

Cathecholamine and 5-hydroxytryptamine levels in ischemic brain. Influence of p-chlorophenylalanine.

The effect of ischemia on catecholamine and 5-hydroxytryptamine (5-HT) levels in brain cortex was examined in the gerbil stroke model. Unilateral common carotid artery occlusion produced bilateral decrease in cortical dopamine levels in gerbils both symptomatic and asymptomatic of cerbral ischemia. The 5-HT progressively decreased only in the occluded hemisphere of ischemic animals. In p-chlorophenylalanine (PCPA)-treated gerbisl, dopamine decreased only in the occluded hemisphere of symptomatic animals, but norepinephrine became decreased bilaterally compared with controls. The 5-HT decrease was twice that seen in untreated animals. It is suggested that these results indicate initial release together with reduced synthesis of monoamines in ischemic brain. The incidence of ischemia induced by carotid occlusion decreased from 44% to 26% in PCPA-treated animals, which also suggests that depletion of 5-HT available for neuronal release prior to the induction of ischemia may reduce stroke incidence by limiting impairment of collateral vasocapacitance. PCPA pretreatment did not influence the development of edema in the occluded hemisphere of ischemic animals once ischemia was established.